Genes involved in the patterning of adult cuticular structures of Drosophila melanogaster have been identified by isolating new mutations that modify the phenotypes of existing mutations in two classes of genes, the segmentation genes that divide the fly into repeating segmental units and the homeotic genes that assign individual identities to each segment. Many of the newly-identified genes encode factors required for transcriptional regulation of the segmentation and homeotic genes. Some of these factors are repressors, but the majority are transcriptional activators. We are investigating both the trans-acting regulatory factors and their cis-acting target sequences in the homeotic genes. Of the two dozen factors identified that are required for activation or function of the homeotic genes, only nine are required for proper functioning of the hedgehog segmentation gene in imaginal tissues. At least three of these nine appear to be tissue-specific regulators of hedgehog transcription. One of the genes that is required for transcription of hedgehog in all of the tissues examined encodes the Drosophila homologue of the yeast remodeling factor SWI2/SNF2. This is the Drosophila brahma gene. Two of the three protein domains conserved between brahma and the yeast SWI2/SNF2 protein are required for brahma function. A third conserved domain, the bromodomain, is not essential in either the yeast or Drosophila proteins. Several brahma-interacting mutations have been isolated and two of the genes transposon-tagged.